In the section on epidemiology, we have shown that cardiovascular disease is the leading cause of death and disability due to illness worldwide.
The key question, therefore, is who should be treated in primary prevention, and what treatment goals should be achieved in secondary prevention.
Primary prevention refers to the treatment of individuals with an elevated cardiovascular risk who have not yet developed cardiovascular disease.
Secondary prevention, on the other hand, refers to the treatment of individuals who already have cardiovascular disease.
Unfortunately, we currently have different guidelines for both primary and secondary prevention, each with varying emphases and target values. This makes it difficult not only for laypeople but also for medical professionals to determine the appropriate treatment for patients.
A detailed discussion of the guidelines and their differences can be found in:
Feingold KR. Guidelines for the Management of High Blood Cholesterol. [Updated 2025 Mar 27]. In: Feingold KR, Ahmed SF, Anawalt B, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK305897/
On this website, we will present the key treatment recommendations that are largely consistent across all major guidelines.
There is a broad consensus that cardiovascular risk can be reduced through lifestyle interventions.
Risk factors for cardiovascular disease include:
Before starting any medication, it is essential to improve these factors through lifestyle changes.
All guidelines agree that LDL cholesterol (LDL-C) is the most important factor in the development of atherosclerosis and cardiovascular disease.
We aim to show who should be treated and how aggressively cholesterol levels should be lowered.
Cholesterol is absorbed from the diet and also produced in the liver in the form of LDL-C..
The most important medications to lower LDL cholesterol are statins. Statins are approved by all health authorities.
They inhibit the HMG-CoA reductase enzyme, which leads to a reduction in LDL cholesterol levels in the blood.
Cholesterol is a fat-like substance that is very important for our body.
It is used, for example, to build cell membranes and produce hormones.
The body obtains cholesterol in two ways:
The starting substance for cholesterol production is Acetyl-CoA,
a small molecule that arises from the breakdown of sugar or fat.
Through several steps, cholesterol is formed from Acetyl-CoA, with the help of enzymes (chemical catalysts).
The most important enzyme in cholesterol synthesis is HMG-CoA reductase.
In addition to statins and ezetimibe, there are other lipid-lowering medications, which are discussed in the section on pharmacological therapy.
Before beginning treatment, a patient’s cardiovascular risk must be assessed.
Treatment and its intensity depend on this risk.
Guidelines differentiate between individuals with:
In Patients with very high risk:
These individuals are considered to have very high cardiovascular risk by default. In such cases, no formal risk estimation is necessary. “Treatment is always recommended.”
The main task is to identify which patients actually benefit from treatment of risk factors for atherosclerotic cardiovascular disease (ASCVD).
Current guidelines for the treatment of cholesterol to reduce cardiovascular risk recommend that the following four groups of patients will benefit from moderate- or high-intensity statin therapy:2
With increasing age, the risk of developing cardiovascular disease (CVD) also rises. Women under the age of 40 have a very low cardiovascular risk, provided there are no additional modifiable risk factors that could increase the long-term risk of a cardiovascular event (CVE). On the other hand, men over 65 and women over 75 almost always have a significantly increased risk of experiencing a cardiovascular event within the next ten years. Treatment is always recommended. Therefore, in healthy individuals, the assessment of whether an intervention or treatment is necessary is limited to the age range of 55 to 75 for women and 40 to 65 for men. Only within this age range do the threshold values for intervention vary in a way that affects the ten-year risk.
The simplest approach is to use the CVD risk calculator :https://clincalc.com/cardiology/ascvd/pooledcohort.aspx.
The required inputs are: sex, age, race, total cholesterol, HDL cholesterol, and systolic blood pressure. Additionally, it must be indicated whether the person is on blood pressure medication, has diabetes, or is a smoker.”
We advise against the PREVENT calculator because it results in a significant number of patients not receiving appropriate treatment.”
The risk calculator helps identify the individual’s risk group and the recommended LDL cholesterol reduction according to the guidelines.
Cholesterol Goals
Very High Risk | LDL-C reduction of >50% from baseline and an LDL-C goal of <1.4 mmol/L (<55 mg/dL) is recommended |
High Risk | LDL-C reduction of >50% from baseline and an LDL-C goal of <1.8 mmol/L (<70 mg/dL) is recommended |
Moderate Risk | LDL-C goal of <2.6 mmol/L (<100 mg/dL) should be considered |
Low Risk | LDL-C goal <3.0 mmol/L (<116 mg/dL) may be considered. |
The risk calculator is derived from studies conducted in the United States. For European populations, the ESC/EAS guidelines provide appropriate recommendations.
„Differences Between AHA/ACC and ESC/EAS Guidelines
DEFINITION OF VERY HIGH RISK
This definition is important because it sets the stage for considering intensive LDL-C lowering and the use of combined drug therapy for LDL-C lowering. AHA/ACC defines very high risk as a history of multiple ASCVD events or of one event + multiple high-risk conditions. This limits the definition of very high risk to the highest risk patients among those with ASCVD. In contrast, ESC/EAS considers all patients with clinical ASCVD or ASCVD on imaging as very high risk. Additionally, ESC/EAS allows extension of the definition to highest risk patients in primary prevention, that is, to patients with multiple risk factors and/or subclinical atherosclerosis (table 9). Overall, more patients will be identified as being at very high risk by ESC/EAS guidelines. This could enlarge the usage of PCSK9 inhibitors. AHA/ACC limits the use of PCSK9 inhibitors to patients at highest risk, because of their high cost. One recent study (43) showed that only about 10% of patients with established ASCVD will be eligible for PCSK9 inhibitors by AHA/ACC recommendations.“
Feingold KR. Guidelines for the Management of High Blood Cholesterol. [Updated 2025 Mar 27]. In: Feingold KR, Ahmed SF, Anawalt B, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK305897/